The goal of this program is to improve the understanding, treatment and survival of patients with malignant lymphoma. We plan to extend our preliminary findings and take advantage of our extensive patient population and tissue bank use and data base. A highly interactive group of investigators will share resources and apply exciting new developments in technology in three general areas. I. Clinical Trials Two clinical trials will be conducted, one for patients with post transplant lymphoproliferative disease and one for patients with mycosis fungoides. These trials will test novel therapeutic approaches developed at Stanford, monoclonal anti CD20 antibody and vaccination with the antigen receptor, respectively. II. Lymphomagenesis The role of hepatitis C virus in B cell activation will be investigated. This is based on the discovery that CD81, a molecule important in B cell signaling and in B cell-T interaction, is a receptor for the hepatitis C CD81, a molecule important in B cell signaling and in B cell-T cell interaction, is a receptor for the hepatitis C virus coat protein. The immunoglobulins from B cell lymphomas which occur in patients infected with HCV will be tested for binding activity against HCV. The role of the Notch signaling pathway is lymphomagenesis will be studied. The Notch1 gene was found to collaborate with the E2A-PBX1 translocation in T cell lymphoma development in mice. An exciting hypothesis is that a ligand for the Notch1 gene plays an important role in suppressing oncogenesis. III. Gene Expression Patterns in Lymphoma DNA microarrays of genes expressed in lymphocytes (Lymphochips) will be used together with powerful informatics tools to develop new approaches to diagnose, predict outcome, understand tumor progression and analyze signaling pathways in lymphoma.